Differential gene expression of IFN-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS.
Human PBMC from HIV-1-infected individuals produced ex vivo in response to vesicular stomatitis virus only low amounts of IFN-alpha. This impairment was significant as early as Walter Reed (WR) stage 2; at WR stage 4-5, the production was almost zero. At WR stage 2 of infection, IFN-alpha mRNA was exclusively found in association with polyribosomes, indicating that IFN-alpha gene was transcriptionally inactive under the experimental conditions used. A similar decrease of the level of transcripts as a function of the progression of the disease was also observed for the IFN-gamma mRNA. In contrast, TNF-alpha production was strongly enhanced in PBMC from HIV-1-infected individuals after stimulation with LPS compared to the TNF-alpha production of activated PBMC from healthy donors. Almost parallel with the increase of the level of the transcript for TNF-alpha, the level of TNF-beta increases as well. Data are presented which show that the increased TNF-alpha production is due to a longer half-life of TNF-alpha transcripts in PBMC from infected individuals. These results let us suggest that the up-regulation of TNF-alpha gene expression in PBMC from HIV-infected individuals is controlled predominantly on the posttranscriptional level, whereas transcriptional events regulate the level of IFN-alpha transcripts. This assumption is supported by run-on experiments which revealed that the extent of transcription of TNF-alpha gene is almost identical in nuclei from stimulated PBMC of noninfected and HIV-infected donors, whereas the transcription of IFN-alpha gene is strongly suppressed in nuclei from HIV-infected individuals at WR stages 3 and 6.
Voth
R
R
Medizinische Klinik and Poliklinik, Klinikum der Universität, Mainz, West Germany.
Rossol
S
S
Klein
K
K
Hess
G
G
Schütt
K H
KH
Schröder
H C
HC
Meyer zum Büschenfelde
K H
KH
Müller
W E
WE
D000386:AIDS-Related Complex / Q000235:genetics*; D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D015152:Blotting, Northern; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D007370:Interferon Type I; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate